tbuckley/cabot-search huggingface dataset:
Fatal Occupational Asthma in Cannabis Production — Massachusetts, 2022
Authors: Virginia M. Weaver, Jeremy T. Hua, Kathleen M. Fitzsimmons, James R. Laing, Wigdan Farah, Anne Hart, Trapper J. Braegger, Michelle Reid, David N. Weissman
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Multiple respiratory hazards have been identified in the cannabis cultivation and production industry, in which occupational asthma and work-related exacerbation of preexisting asthma have been reported. An employee working in a Massachusetts cannabis cultivation and processing facility experienced progressively worsening work-associated respiratory symptoms, which culminated in a fatal asthma attack in January 2022. This report represents findings of an Occupational Safety and Health Administration inspection, which included a worksite exposure assessment, coworker and next-of-kin interviews, medical record reviews, and collaboration with the Massachusetts Department of Public Health. Respiratory tract or skin symptoms were reported by four of 10 coworkers with similar job duties. Prevention is best achieved through a multifaceted approach, including controlling asthmagen exposures, such as cannabis dust, providing worker training, and conducting medical monitoring for occupational allergy. Evaluation of workers with new-onset or worsening asthma is essential, along with prompt diagnosis and medical management, which might include cessation of work and workers' compensation when relation to work exposures is identified. It is important to recognize that work in cannabis production is potentially causative.
2023 American Heart Association and American Academy of Pediatrics Focused Update on Neonatal Resuscitation: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Authors: Nicole K. Yamada, Edgardo Szyld, Marya L. Strand, Emer Finan, Jessica L. Illuzzi, Beena D. Kamath-Rayne, Vishal S. Kapadia, Susan Niermeyer, Georg M. Schmölzer, Amanda Williams, Gary M. Weiner, Myra H. Wyckoff, Henry C. Lee
Journal: Circulation (2023)

This 2023 focused update to the neonatal resuscitation guidelines is based on 4 systematic reviews recently completed under the direction of the International Liaison Committee on Resuscitation Neonatal Life Support Task Force. Systematic reviewers and content experts from this task force performed comprehensive reviews of the scientific literature on umbilical cord management in preterm, late preterm, and term newborn infants, and the optimal devices and interfaces used for administering positive-pressure ventilation during resuscitation of newborn infants. These recommendations provide new guidance on the use of intact umbilical cord milking, device selection for administering positive-pressure ventilation, and an additional primary interface for administering positive-pressure ventilation.
Clinical Validation of Human Papilloma Virus Circulating Tumor DNA for Early Detection of Residual Disease After Chemoradiation in Cervical Cancer
Authors: Kathy Han, Jinfeng Zou, Zhen Zhao, Zeynep Baskurt, Yangqiao Zheng, Elizabeth Barnes, Jennifer Croke, Sarah E. Ferguson, Anthony Fyles, Lilian Gien, Adam Gladwish, Magali Lecavalier-Barsoum, Stephanie Lheureux, Jelena Lukovic, Helen Mackay, Eve-Lyne Marchand, Ur Metser, Michael Milosevic, Amandeep S. Taggar, Scott V. Bratman, Eric Leung
Journal: Journal of Clinical Oncology (2023)

Most cervical cancers are caused by human papilloma virus (HPV), and HPV circulating tumor DNA (ctDNA) may identify patients at highest risk of relapse. Our pilot study using digital polymerase chain reaction (dPCR) showed that detectable HPV ctDNA at the end of chemoradiation (CRT) is associated with inferior progression-free survival (PFS) and that a next-generation sequencing approach (HPV-seq) may outperform dPCR. We aimed to prospectively validate HPV ctDNA as a tool for early detection of residual disease.
A study of generative large language model for medical research and healthcare
Authors: Cheng Peng, Xi Yang, Aokun Chen, Kaleb E. Smith, Nima PourNejatian, Anthony B. Costa, Cheryl Martin, Mona G. Flores, Ying Zhang, Tanja Magoc, Gloria Lipori, Duane A. Mitchell, Naykky S. Ospina, Mustafa M. Ahmed, William R. Hogan, Elizabeth A. Shenkman, Yi Guo, Jiang Bian, Yonghui Wu
Journal: npj Digital Medicine (2023)

Abstract There are enormous enthusiasm and concerns in applying large language models (LLMs) to healthcare. Yet current assumptions are based on general-purpose LLMs such as ChatGPT, which are not developed for medical use. This study develops a generative clinical LLM, GatorTronGPT, using 277 billion words of text including (1) 82 billion words of clinical text from 126 clinical departments and approximately 2 million patients at the University of Florida Health and (2) 195 billion words of diverse general English text. We train GatorTronGPT using a GPT-3 architecture with up to 20 billion parameters and evaluate its utility for biomedical natural language processing (NLP) and healthcare text generation. GatorTronGPT improves biomedical natural language processing. We apply GatorTronGPT to generate 20 billion words of synthetic text. Synthetic NLP models trained using synthetic text generated by GatorTronGPT outperform models trained using real-world clinical text. Physicians’ Turing test using 1 (worst) to 9 (best) scale shows that there are no significant differences in linguistic readability ( p = 0.22; 6.57 of GatorTronGPT compared with 6.93 of human) and clinical relevance ( p = 0.91; 7.0 of GatorTronGPT compared with 6.97 of human) and that physicians cannot differentiate them ( p &lt; 0.001). This study provides insights into the opportunities and challenges of LLMs for medical research and healthcare.
Gut microbiome in healthy aging versus those associated with frailty
Authors: Mi Young Lim, Young-Do Nam
Journal: Gut Microbes (2023)

As the proportion of older people in the world's population steadily increases, there is an urgent need to identify ways to support healthy aging. The gut microbiome has been proposed to be involved in aging-related diseases and has become an attractive target for improving health in older people. Herein, we cover the relationship between the gut microbiome and chronological age in adults, and then, we discuss the gut microbiome features associated with frailty, as a hallmark of unhealthy aging in older people. Furthermore, we describe the effects of microbiome-targeted interventions, such as dietary patterns and consumption of probiotics, prebiotics, and synbiotics, on modulating the gut microbiome composition and further promoting healthy aging. Further studies are needed to explore the underlying mechanisms of gut microbiome-induced aging complications and to develop personalized microbiome-based strategies for reducing the severity of frailty or preventing the onset of frailty in older adults.
A phase 1 open-label pilot study of low-dose interleukine-2 immunotherapy in patients with Alzheimer’s disease
Authors: Alireza Faridar, Abdulmunaim M. Eid, Aaron D. Thome, Weihua Zhao, David R. Beers, Maria B. Pascual, Mohammad O. Nakawah, Gustavo C. Roman, Charles S. Davis, Michael Grundman, Joseph C. Masdeu, Stanley H. Appel
Journal: Translational Neurodegeneration (2023)

Trial registration ClinicalTrials.gov Identifier: NCT05821153, Registered April 20 2023, Retrospectively registered, https://classic.clinicaltrials.gov/ct2/show/NCT05821153
Multi-modal proteomic characterization of lysosomal function and proteostasis in progranulin-deficient neurons
Authors: Saadia Hasan, Michael S. Fernandopulle, Stewart W. Humble, Ashley M. Frankenfield, Haorong Li, Ryan Prestil, Kory R. Johnson, Brent J. Ryan, Richard Wade-Martins, Michael E. Ward, Ling Hao
Journal: Molecular Neurodegeneration (2023)

Abstract Background Progranulin (PGRN) is a lysosomal glycoprotein implicated in various neurodegenerative diseases, including frontotemporal dementia and neuronal ceroid lipofuscinosis. Over 70 mutations discovered in the GRN gene all result in reduced expression of the PGRN protein. Genetic and functional studies point toward a regulatory role for PGRN in lysosome functions. However, the detailed molecular function of PGRN within lysosomes and the impact of PGRN deficiency on lysosomes remain unclear. Methods We developed multifaceted proteomic techniques to characterize the dynamic lysosomal biology in living human neurons and fixed mouse brain tissues. Using lysosome proximity labeling and immuno-purification of intact lysosomes, we characterized lysosome compositions and interactome in both human induced pluripotent stem cell (iPSC)-derived glutamatergic neurons (i 3 Neurons) and mouse brains. Using dynamic stable isotope labeling by amino acids in cell culture (dSILAC) proteomics, we measured global protein half-lives in human i 3 Neurons for the first time. Results Leveraging the multi-modal proteomics and live-cell imaging techniques, we comprehensively characterized how PGRN deficiency changes the molecular and functional landscape of neuronal lysosomes. We found that PGRN loss impairs the lysosome’s degradative capacity with increased levels of v-ATPase subunits on the lysosome membrane, increased hydrolases within the lysosome, altered protein regulations related to lysosomal transport, and elevated lysosomal pH. Consistent with impairments in lysosomal function, GRN -null i 3 Neurons and frontotemporal dementia patient-derived i 3 Neurons carrying GRN mutation showed pronounced alterations in protein turnover, such as cathepsins and proteins related to supramolecular polymerization and inherited neurodegenerative diseases. Conclusion This study suggested PGRN as a critical regulator of lysosomal pH and degradative capacity, which influences global proteostasis in neurons. Beyond the study of progranulin deficiency, these newly developed proteomic methods in neurons and brain tissues provided useful tools and data resources for the field to study the highly dynamic neuronal lysosome biology. Graphical Abstract
Blood‐derived product therapies for SARS‐CoV‐2 infection and long COVID
Authors: Junzheng Wu, Huichuan Yang, Ding Yu, Xiaoming Yang
Journal: MedComm (2023)

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is capable of large‐scale transmission and has caused the coronavirus disease 2019 (COVID‐19) pandemic. Patients with COVID‐19 may experience persistent long‐term health issues, known as long COVID. Both acute SARS‐CoV‐2 infection and long COVID have resulted in persistent negative impacts on global public health. The effective application and development of blood‐derived products are important strategies to combat the serious damage caused by COVID‐19. Since the emergence of COVID‐19, various blood‐derived products that target or do not target SARS‐CoV‐2 have been investigated for therapeutic applications. SARS‐CoV‐2‐targeting blood‐derived products, including COVID‐19 convalescent plasma, COVID‐19 hyperimmune globulin, and recombinant anti‐SARS‐CoV‐2 neutralizing immunoglobulin G, are virus‐targeting and can provide immediate control of viral infection in the short term. Non‐SARS‐CoV‐2‐targeting blood‐derived products, including intravenous immunoglobulin and human serum albumin exhibit anti‐inflammatory, immunomodulatory, antioxidant, and anticoagulatory properties. Rational use of these products can be beneficial to patients with SARS‐CoV‐2 infection or long COVID. With evidence accumulated since the pandemic began, we here summarize the progress of blood‐derived product therapies for COVID‐19, discuss the effective methods and scenarios regarding these therapies, and provide guidance and suggestions for clinical treatment.
Diagnostic Potential of Oscillometry: A Population-based Approach
Authors: Chiara Veneroni, Christoph Valach, Emiel F. M. Wouters, Alessandro Gobbi, Raffaele L. Dellacà, Marie-Kathrin Breyer, Sylvia Hartl, Owat Sunanta, Charles G. Irvin, Caspar Schiffers, Pasquale Pio Pompilio, Robab Breyer-Kohansal
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Respiratory resistance (Rrs) and reactance (Xrs) as measured by oscillometry and their intrabreath changes have emerged as sensitive parameters for detecting early pathological impairments during tidal breathing.
Specific Inhibition of Orai1-mediated Calcium Signalling Resolves Inflammation and Clears Bacteria in an Acute Respiratory Distress Syndrome Model
Authors: Saira Ahmad, Joe A. Wrennall, Alexandra S. Goriounova, Malika Sekhri, Jason A. Iskarpatyoti, Arunava Ghosh, Sabri H. Abdelwahab, Alexis Voeller, Mani Rai, Rahul Y. Mahida, Krzysztof Krajewski, Diane M. Ignar, Alon Greenbaum, Timothy P. Moran, Stephen L. Tilley, David R. Thickett, M. Flori Sassano, Robert Tarran
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Rationale: Acute respiratory distress syndrome (ARDS) has an unacceptably high mortality rate (35%) and is without effective therapy. Orai1 is a Ca2+ channel involved in store-operated Ca2+ entry (SOCE), a process that exquisitely regulates inflammation. Orai1 is considered a druggable target, but no Orai1-specific inhibitors exist to date. Objectives: To evaluate whether ELD607, a first-in-class Orai1 antagonist, can treat ARDS caused by bacterial pneumonia in preclinical models. Methods: ELD607 pharmacology was evaluated in HEK293T cells and freshly isolated immune cells from patients with ARDS. A murine acute lung injury model caused by bacterial pneumonia was then used: mice were infected with Pseudomonas aeruginosa, Staphylococcus aureus, methicillin-resistant S. aureus, or multidrug-resistant P. aeruginosa and then treated with ELD607 intranasally. Measurements and Main Results: ELD607 specifically inhibited SOCE in HEK293T cells with a half-maximal inhibitory concentration of 9 nM. ELD607 was stable in ARDS airway secretions and inhibited SOCE in ARDS immune cells. In vivo, inhaled ELD607 significantly reduced neutrophilia and improved survival. Surprisingly, Orai1 inhibition by ELD607 caused a significant reduction in lung bacteria, including methicillin-resistant S. aureus. ELD607 worked as an immunomodulator that reduced cytokine levels, reduced neutrophilia, and promoted macrophage-mediated resolution of inflammation and clearance of bacteria. Indeed, when alveolar macrophages were depleted with inhaled clodronate, ELD607 was no longer able to resolve inflammation or clear bacteria. Conclusions: These data indicate that specific Orai1 inhibition by ELD607 may be a novel approach to reduce multiorgan inflammation and treat antibiotic-resistant bacteria.
Cumulative Absolute Risk of Subsequent Colorectal Cancer After Abdominopelvic Radiotherapy Among Childhood Cancer Survivors: A PanCareSurFup Study
Authors: Emma J. Heymer, Katarzyna Jóźwiak, Leontien C. Kremer, David L. Winter, Florent de Vathaire, Ceren Sunguc, Elaine Sugden, Judith L. Kok, Helena J.H. van der Pal, Lars Hjorth, Zsuzsanna Jakab, Milena M. Maule, Riccardo Haupt, Francesca Bagnasco, Monica Terenziani, Ibrahima Diallo, Maria W. Gunnes, Grit Sommer, Lorna Zadravec Zaletel, Claudia E. Kuehni, Jeanette F. Winther, Päivi M. Lähteenmäki, Thorgerdur Gudmundsdottir, Rodrigue S. Allodji, Roderick Skinner, Cécile M. Ronckers, Michael M. Hawkins, Raoul C. Reulen, Jop C. Teepen
Journal: Journal of Clinical Oncology (2023)

Childhood cancer survivors are at the risk of developing subsequent colorectal cancers (CRCs), but the absolute risks by treatment modality are uncertain. We quantified the absolute risks by radiotherapy treatment characteristics using clinically accessible data from a Pan-European wide case-control study nested within a large cohort of childhood cancer survivors: the PanCareSurFup Study.
Opioid tapering in older cancer survivors does not increase psychiatric or drug hospitalization rates
Authors: Paul Riviere, Kylie M Morgan, Leah N Deshler, Xinyi Huang, Carla Marienfeld, Christopher J Coyne, Brent S Rose, James D Murphy
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Opioid tapering in the general population is linked to increases in hospitalizations or emergency department visits related to psychiatric or drug-related diagnoses. Cancer survivors represent a unique population with different opioid indications, prescription patterns, and more frequent follow-up care. This study sought to describe patterns of opioid tapering among older cancer survivors and to test the hypothesis of whether older cancer survivors face increased risks of adverse events with opioid tapering. Methods Using the Surveillance, Epidemiology and End Results Medicare–linked database, we identified 15 002 Medicare-beneficiary cancer survivors diagnosed between 2010 and 2017 prescribed opioids consistently for at least 6 months after their cancer diagnosis. Tapering was defined as a binary time-varying event occurring with any monthly oral morphine equivalent reduction of 15% or more from the previous month. Primary diagnostic billing codes associated with emergency room or hospital admissions were used for the composite endpoint of psychiatric- or drug-related event(s). Results There were 3.86 events per 100 patient-months, with 97.8% events being mental health emergencies, 1.91% events being overdose emergencies, and 0.25% involving both. Using a generalized estimating equation for repeated measure time-based analysis, opioid tapering was not statistically associated with acute events in the 3-month posttaper period (odds ratio [OR] = 1.02; P = .62) or at any point in the future (OR = 0.96; P = .46). Conclusions Opioid tapering in older cancer survivors does not appear to be linked to a higher risk of acute psychiatric- or drug-related events, in contrast to prior research in the general population.
Clonal selection of hematopoietic stem cells after gene therapy for sickle cell disease
Authors: Michael Spencer Chapman, Alyssa H. Cull, Marioara F. Ciuculescu, Erica B. Esrick, Emily Mitchell, Hyunchul Jung, Laura O’Neill, Kirsty Roberts, Margarete A. Fabre, Nicholas Williams, Jyoti Nangalia, Joanne Quinton, James M. Fox, Danilo Pellin, Julie Makani, Myriam Armant, David A. Williams, Peter J. Campbell, David G. Kent
Journal: Nature Medicine (2023)

Abstract Gene therapy (GT) provides a potentially curative treatment option for patients with sickle cell disease (SCD); however, the occurrence of myeloid malignancies in GT clinical trials has prompted concern, with several postulated mechanisms. Here, we used whole-genome sequencing to track hematopoietic stem cells (HSCs) from six patients with SCD at pre- and post-GT time points to map the somatic mutation and clonal landscape of gene-modified and unmodified HSCs. Pre-GT, phylogenetic trees were highly polyclonal and mutation burdens per cell were elevated in some, but not all, patients. Post-GT, no clonal expansions were identified among gene-modified or unmodified cells; however, an increased frequency of potential driver mutations associated with myeloid neoplasms or clonal hematopoiesis ( DNMT3A - and EZH2 -mutated clones in particular) was observed in both genetically modified and unmodified cells, suggesting positive selection of mutant clones during GT. This work sheds light on HSC clonal dynamics and the mutational landscape after GT in SCD, highlighting the enhanced fitness of some HSCs harboring pre-existing driver mutations. Future studies should define the long-term fate of mutant clones, including any contribution to expansions associated with myeloid neoplasms.
The unequal effects of the health–economy trade-off during the COVID-19 pandemic
Authors: Marco Pangallo, Alberto Aleta, R. Maria del Rio-Chanona, Anton Pichler, David Martín-Corral, Matteo Chinazzi, François Lafond, Marco Ajelli, Esteban Moro, Yamir Moreno, Alessandro Vespignani, J. Doyne Farmer
Journal: Nature Human Behaviour (2023)

Despite the global impact of the coronavirus disease 2019 pandemic, the question of whether mandated interventions have similar economic and public health effects as spontaneous behavioural change remains unresolved. Addressing this question, and understanding differential effects across socioeconomic groups, requires building quantitative and fine-grained mechanistic models. Here we introduce a data-driven, granular, agent-based model that simulates epidemic and economic outcomes across industries, occupations and income levels. We validate the model by reproducing key outcomes of the first wave of coronavirus disease 2019 in the New York metropolitan area. The key mechanism coupling the epidemic and economic modules is the reduction in consumption due to fear of infection. In counterfactual experiments, we show that a similar trade-off between epidemic and economic outcomes exists both when individuals change their behaviour due to fear of infection and when non-pharmaceutical interventions are imposed. Low-income workers, who perform in-person occupations in customer-facing industries, face the strongest trade-off.
Prospective implementation of AI-assisted screen reading to improve early detection of breast cancer
Authors: Annie Y. Ng, Cary J. G. Oberije, Éva Ambrózay, Endre Szabó, Orsolya Serfőző, Edit Karpati, Georgia Fox, Ben Glocker, Elizabeth A. Morris, Gábor Forrai, Peter D. Kecskemethy
Journal: Nature Medicine (2023)

Abstract Artificial intelligence (AI) has the potential to improve breast cancer screening; however, prospective evidence of the safe implementation of AI into real clinical practice is limited. A commercially available AI system was implemented as an additional reader to standard double reading to flag cases for further arbitration review among screened women. Performance was assessed prospectively in three phases: a single-center pilot rollout, a wider multicenter pilot rollout and a full live rollout. The results showed that, compared to double reading, implementing the AI-assisted additional-reader process could achieve 0.7–1.6 additional cancer detection per 1,000 cases, with 0.16–0.30% additional recalls, 0–0.23% unnecessary recalls and a 0.1–1.9% increase in positive predictive value (PPV) after 7–11% additional human reads of AI-flagged cases (equating to 4–6% additional overall reading workload). The majority of cancerous cases detected by the AI-assisted additional-reader process were invasive (83.3%) and small-sized (≤10 mm, 47.0%). This evaluation suggests that using AI as an additional reader can improve the early detection of breast cancer with relevant prognostic features, with minimal to no unnecessary recalls. Although the AI-assisted additional-reader workflow requires additional reads, the higher PPV suggests that it can increase screening effectiveness.
Wireless broadband acousto-mechanical sensing system for continuous physiological monitoring
Authors: Jae-Young Yoo, Seyong Oh, Wissam Shalish, Woo-Youl Maeng, Emily Cerier, Emily Jeanne, Myung-Kun Chung, Shasha Lv, Yunyun Wu, Seonggwang Yoo, Andreas Tzavelis, Jacob Trueb, Minsu Park, Hyoyoung Jeong, Efe Okunzuwa, Slobodanka Smilkova, Gyeongwu Kim, Junha Kim, Gooyoon Chung, Yoonseok Park, Anthony Banks, Shuai Xu, Guilherme M. Sant’Anna, Debra E. Weese-Mayer, Ankit Bharat, John A. Rogers
Journal: Nature Medicine (2023)